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Properdin

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https://www.readbyqxmd.com/read/28196665/complement-s-hidden-arsenal-new-insights-and-novel-functions-inside-the-cell
#1
M Kathryn Liszewski, Michelle Elvington, Hrishikesh S Kulkarni, John P Atkinson
A key component of both innate and adaptive immunity, new understandings of the complement system are expanding its roles beyond that traditionally appreciated. Evidence is accumulating that complement has an intracellular arsenal of components that provide not only immune defense, but also assist in key interactions for host cell functions. Although early work has primarily centered on T cells, the intracellular complement system likely functions in many if not most cells of the body. Some of these functions may trace their origins to the primitive complement system that began as a primeval form of C3 likely tasked for protection from intracellular pathogen invasion...
February 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28195242/the-alternative-complement-pathway-is-dysregulated-in-patients-with-chronic-heart-failure
#2
Negar Shahini, Annika E Michelsen, Per H Nilsson, Karin Ekholt, Lars Gullestad, Kaspar Broch, Christen P Dahl, Pål Aukrust, Thor Ueland, Tom Eirik Mollnes, Arne Yndestad, Mieke C Louwe
The complement system, an important arm of the innate immune system, is activated in heart failure (HF). We hypothesized that HF patients are characterized by an imbalance of alternative amplification loop components; including properdin and complement factor D and the alternative pathway inhibitor factor H. These components and the activation product, terminal complement complex (TCC), were measured in plasma from 188 HF patients and 67 age- and sex- matched healthy controls by enzyme immunoassay. Our main findings were: (i) Compared to controls, patients with HF had significantly increased levels of factor D and TCC, and decreased levels of properdin, particularly patients with advanced clinical disorder (i...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28139294/c5-inhibition-prevents-renal-failure-in-a-mouse-model-of-lethal-c3-glomerulopathy
#3
Allison Lesher Williams, Damodar Gullipalli, Yoshiyasu Ueda, Sayaka Sato, Lin Zhou, Takashi Miwa, Kenneth S Tung, Wen-Chao Song
C3 glomerulopathy is a potentially life-threatening disease of the kidney caused by dysregulated alternative pathway complement activation. The specific complement mediator(s) responsible for kidney injury in C3 glomerulopathy are yet to be defined and no specific therapy is currently available. We previously developed a mouse model of lethal C3 glomerulopathy with factor H and properdin gene double mutations. Therefore, we used this model to examine the role of C5 and C5a receptor (C5aR) in the pathogenesis of the disease...
January 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28105653/properdin-and-factor-h-production-by-human-dendritic-cells-modulates-their-t-cell-stimulatory-capacity-and-is-regulated-by-ifn-%C3%AE
#4
Karen O Dixon, Joseph O'Flynn, Ngaisah Klar-Mohamad, Mohamed R Daha, Cees van Kooten
Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T-cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs...
January 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28104543/a-review-of-human-diseases-caused-or-exacerbated-by-aberrant-complement-activation
#5
REVIEW
Patrick L McGeer, Moonhee Lee, Edith G McGeer
Complement is the backbone of our innate immune system. It is of ancient evolutionary origin, being traced back to horseshoe crabs 350 million years ago. It consists today of more than 25 proteins which must work together like clockwork to distinguish friend from foe. Self-attack by the complement system can occur whenever it fails to do so. This failure has been reported to occur in an estimated 22 human diseases. A significant number of these are chronic degenerative neurological disorders. In some, there is overwhelming evidence that complement self-attack causes the disease...
December 27, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28086806/age-related-macular-degeneration-associated-polymorphism-rs10490924-in-arms2-results-in-deficiency-of-a-complement-activator
#6
Sven Micklisch, Yuchen Lin, Saskia Jacob, Marcus Karlstetter, Katharina Dannhausen, Prasad Dasari, Monika von der Heide, Hans-Martin Dahse, Lisa Schmölz, Felix Grassmann, Medhanie Alene, Sascha Fauser, Harald Neumann, Stefan Lorkowski, Diana Pauly, Bernhard H Weber, Antonia M Joussen, Thomas Langmann, Peter F Zipfel, Christine Skerka
BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The polymorphism rs10490924 in the ARMS2 gene is highly associated with AMD and linked to an indel mutation (del443ins54), the latter inducing mRNA instability. At present, the function of the ARMS2 protein, the exact cellular sources in the retina and the biological consequences of the rs10490924 polymorphism are unclear. METHODS: Recombinant ARMS2 was expressed in Pichia pastoris, and protein functions were studied regarding cell surface binding and complement activation in human serum using fluoresence-activated cell sorting (FACS) as well as laser scanning microscopy (LSM)...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28069958/properdin-binding-to-complement-activating-surfaces-depends-on-initial-c3b-deposition
#7
Morten Harboe, Christina Johnson, Stig Nymo, Karin Ekholt, Camilla Schjalm, Julie K Lindstad, Anne Pharo, Bernt Christian Hellerud, Kristina Nilsson Ekdahl, Tom Eirik Mollnes, Per H Nilsson
Two functions have been assigned to properdin; stabilization of the alternative convertase, C3bBb, is well accepted, whereas the role of properdin as pattern recognition molecule is controversial. The presence of nonphysiological aggregates in purified properdin preparations and experimental models that do not allow discrimination between the initial binding of properdin and binding secondary to C3b deposition is a critical factor contributing to this controversy. In previous work, by inhibiting C3, we showed that properdin binding to zymosan and Escherichia coli is not a primary event, but rather is solely dependent on initial C3 deposition...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28052346/properdin-deficiency-protects-from-5-fluorouracil-induced-small-intestinal-mucositis-in-a-complement-activation-independent-il-10-dependent-mechanism
#8
Umang Jain, Craig A Midgen, Trent M Woodruff, Wilhelm J Schwaeble, Cordula M Stover, Andrew W Stadnyk
Intestinal mucositis is a serious complication of chemotherapy that leads to significant morbidity that may require dose or drug adjustments. Specific mitigating strategies for mucositis are unavailable, partly due to an incomplete understanding of the pathogenic mechanisms. We have previously shown an effect of properdin, a positive regulator of complement activation, in models of colitis. Here we use properdin deficient (P(KO) ) mice to interrogate the role of properdin and complement in small intestinal mucositis...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27864148/three-pentraxins-c-reactive-protein-serum-amyloid-p-component-and-pentraxin-3-mediate-complement-activation-using-collectin-cl-p1
#9
Nitai Roy, Katsuki Ohtani, Yoshihiko Hidaka, Yoshiro Amano, Yasuyuki Matsuda, Kenichiro Mori, Insu Hwang, Norimitsu Inoue, Nobutaka Wakamiya
BACKGROUND: Pentraxins (PTXs) are a superfamily of multifunctional conserved proteins involved in acute-phase responses. Recently, we have shown that collectin placenta 1 (CL-P1) and C-reactive protein (CRP) mediated complement activation and failed to form terminal complement complex (TCC) in normal serum conditions because of complement factor H inhibition. METHODS: We used CL-P1 expressing CHO/ldlA7 cells to study the interaction with PTXs. Soluble type CL-P1 was used in an ELISA assay for the binding, C3 and TCC deposition experiments...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27849512/a-fatal-case-of-invasive-infection-caused-by-w135-neisseria-meningitidis-in-a-vaccinated-french-soldier
#10
Sandrine Duron, Christophe Martinaud, David Lacassagne, Jean-Louis Koeck
We report on the case of fatal "purpura fulminans" caused by Neisseria meningitidis W135 that occurred in a young French soldier vaccinated a few months earlier with the tetravalent conjugate vaccine ACYW135. Biological investigations revealed adequate titers of postvaccination antibodies against serogroups A, C, and W135 and led to the post-mortem diagnosis of a complete C7 complement deficiency. Late complement component deficiency is a well-known risk factor of meningococcal diseases, but usually exposes to recurrent mild infections, whereas severe invasive meningococcal diseases are more likely to occur among properdin-deficient patients...
November 2016: Military Medicine
https://www.readbyqxmd.com/read/27824045/hybrid-mass-spectrometry-approaches-in-glycoprotein-analysis-and-their-usage-in-scoring-biosimilarity
#11
Yang Yang, Fan Liu, Vojtech Franc, Liem Andhyk Halim, Huub Schellekens, Albert J R Heck
Many biopharmaceutical products exhibit extensive structural micro-heterogeneity due to an array of co-occurring post-translational modifications. These modifications often effect the functionality of the product and therefore need to be characterized in detail. Here, we present an integrative approach, combining two advanced mass spectrometry-based methods, high-resolution native mass spectrometry and middle-down proteomics, to analyse this micro-heterogeneity. Taking human erythropoietin and the human plasma properdin as model systems, we demonstrate that this strategy bridges the gap between peptide- and protein-based mass spectrometry platforms, providing the most complete profiling of glycoproteins...
November 8, 2016: Nature Communications
https://www.readbyqxmd.com/read/27811836/recommendations-for-use-of-meningococcal-conjugate-vaccines-in-hiv-infected-persons-advisory-committee-on-immunization-practices-2016
#12
Jessica R MacNeil, Lorry G Rubin, Monica Patton, Ismael R Ortega-Sanchez, Stacey W Martin
At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection. ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease (1), including persons who have persistent (e...
November 4, 2016: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/27782331/properdin-a-tightly-regulated-critical-inflammatory-modulator
#13
REVIEW
Adam Z Blatt, Sabina Pathan, Viviana P Ferreira
The complement alternative pathway is a powerful arm of the innate immune system that enhances diverse inflammatory responses in the human host. Key to the effects of the alternative pathway is properdin, a serum glycoprotein that can both initiate and positively regulate alternative pathway activity. Properdin is produced by many different leukocyte subsets and circulates as cyclic oligomers of monomeric subunits. While the formation of non-physiological aggregates in purified properdin preparations and the presence of potential properdin inhibitors in serum have complicated studies of its function, properdin has, regardless, emerged as a key player in various inflammatory disease models...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27782329/complement-in-removal-of-the-dead-balancing-inflammation
#14
REVIEW
Myriam Martin, Anna M Blom
Recognition and removal of apoptotic and necrotic cells must be efficient and highly controlled to avoid excessive inflammation and autoimmune responses to self. The complement system, a crucial part of innate immunity, plays an important role in this process. Thus, apoptotic and necrotic cells are recognized by complement initiators such as C1q, mannose binding lectin, ficolins, and properdin. This triggers complement activation and opsonization of cells with fragments of C3b, which enhances phagocytosis and thus ensures silent removal...
November 2016: Immunological Reviews
https://www.readbyqxmd.com/read/27777575/activation-of-human-complement-system-by-dextran-coated-iron-oxide-nanoparticles-is-not-affected-by-dextran-fe-ratio-hydroxyl-modifications-and-crosslinking
#15
Guankui Wang, Fangfang Chen, Nirmal K Banda, V Michael Holers, LinPing Wu, S Moein Moghimi, Dmitri Simberg
While having tremendous potential as therapeutic and imaging tools, the clinical use of engineered nanoparticles has been associated with serious safety concerns. Activation of the complement cascade and the release of proinflammatory factors C3a and C5a may contribute to infusion-related reactions, whereas opsonization with C3 fragments promotes rapid recognition and clearance of nanomaterials by mononuclear phagocytes. We used dextran-coated superparamagnetic iron oxide nanoparticles (SPIO), which are potent activators of the complement system, to study the role of nanoparticle surface chemistry in inciting complement in human serum...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27756886/properdistatin-inhibits-angiogenesis-and-improves-vascular-function-in-human-melanoma-xenografts-with-low-thrombospondin-1-expression
#16
Jon-Vidar Gaustad, Trude G Simonsen, Lise Mari K Andersen, Einar K Rofstad
In this study, the effect of properdistatin, a novel peptide derived from the thrombospondin 1 (TSP-1) domain of properdin, was investigated in three melanoma xenograft models with different TSP-1 expression. The tumors were grown in dorsal window chambers and were treated with 80 mg/kg/day properdistatin or vehicle. Morphological parameters of the tumor vasculature were assessed from high resolution transillumination images. Blood supply time (i.e., the time required for arterial blood to flow from a supplying artery to downstream microvessels) and plasma velocities were assessed from first-pass imaging movies recorded after a bolus of fluorescence-labeled dextran had been administered intravenously...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27573083/recommendations-for-serogroup-b-meningococcal-vaccine-for-persons-10-years-and-older
#17
(no author information available yet)
This policy statement provides recommendations for the prevention of serogroup B meningococcal disease through the use of 2 newly licensed serogroup B meningococcal vaccines: MenB-FHbp (Trumenba; Wyeth Pharmaceuticals, a subsidiary of Pfizer, Philadelphia, PA) and MenB-4C (Bexsero; Novartis Vaccines, Siena, Italy). Both vaccines are approved for use in persons 10 through 25 years of age. MenB-FHbp is licensed as a 2- or 3-dose series, and MenB-4C is licensed as a 2-dose series for all groups. Either vaccine is recommended for routine use in persons 10 years and older who are at increased risk of serogroup B meningococcal disease (category A recommendation)...
2016: Pediatrics
https://www.readbyqxmd.com/read/27515662/saliva-of-rhipicephalus-boophilus-microplus-acari-ixodidae-inhibits-classical-and-alternative-complement-pathways
#18
Naylene C S Silva, Vladimir F Vale, Paula F Franco, Nelder F Gontijo, Jesus G Valenzuela, Marcos H Pereira, Mauricio R V Sant'Anna, Daniel S Rodrigues, Walter S Lima, Blima Fux, Ricardo N Araujo
BACKGROUND: Rhipicephalus (Boophilus) microplus is the main ectoparasite affecting livestock worldwide. For a successful parasitism, ticks need to evade several immune responses of their hosts, including the activation of the complement system. In spite of the importance of R. microplus, previous work only identified one salivary molecule that blocks the complement system. The current study describes complement inhibitory activities induced by R. microplus salivary components and mechanisms elicited by putative salivary proteins on both classical and alternative complement pathways...
2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27495980/strong-predictive-value-of-mannose-binding-lectin-levels-for-cardiovascular-risk-of-hemodialysis-patients
#19
Felix Poppelaars, Mariana Gaya da Costa, Stefan P Berger, Solmaz Assa, Anita H Meter-Arkema, Mohamed R Daha, Willem J van Son, Casper F M Franssen, Marc A J Seelen
BACKGROUND: Hemodialysis patients have higher rates of cardiovascular morbidity and mortality compared to the general population. Mannose-binding lectin (MBL) plays an important role in the development of cardiovascular disease. In addition, hemodialysis alters MBL concentration and functional activity. The present study determines the predictive value of MBL levels for future cardiac events (C-event), cardiovascular events (CV-event) and all-cause mortality in HD patients. METHODS: We conducted a prospective study of 107 patients on maintenance hemodialysis...
2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27389986/genes-regulated-by-potassium-channel-tetramerization-domain-containing-15-kctd15-in-the-developing-neural-crest
#20
Thomas C B Wong, Martha Rebbert, Chengdong Wang, Xiongfong Chen, Alison Heffer, Valeria E Zarelli, Igor B Dawid, Hui Zhao
Neural crest (NC) development is controlled precisely by a regulatory network with multiple signaling pathways and the involvement of many genes. The integration and coordination of these factors are still incompletely understood. Overexpression of Wnt3a and the BMP antagonist Chordin in animal cap cells from Xenopus blastulae induces a large number of NC specific genes. We previously suggested that Potassium Channel Tetramerization Domain containing 15 (Kctd15) regulates NC formation by affecting Wnt signaling and the activity of transcription factor AP-2...
2016: International Journal of Developmental Biology
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